Reaction Steps
4-Methoxyphenylhydrazine hydrochloride (3.88 kg, 21.8 mol) and K2CO3 (3.21 kg, 23.2 mol) were added to a THF/EtOAc solution containing (Z)-1-(3,4-dichlorophenyl)-3-hydroxy-4-[(tetrahydro-2H-pyran-2-yl)oxy]-2-buten-1-one (Example 514) at 0-10° C. The resultant suspension was stirred and allowed to warm to rt overnight (16 h). When HPLC analysis indicated the disappearance of the starting material, the reaction mixture was filtered. The organic reaction filtrate was washed with 1 M aq. citric acid (34.0 L), followed by 10% aq. NaCl (50.0 L) and the resulting product solution was used in the next synthetic step without isolation. HPLC (Method U): Rt=16.22 min. MS (ES+): mass calculated for C22H22Cl2N2O3, 432.10; m/z found, 455.1 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.39 (d, J=1.9 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.19 (dd, J=6.8, 2.2 Hz, 2H), 6.96 (dd, J=8.1, 2.1 Hz, 1H), 6.87 (dd, J=2.1, 7 Hz, 2H), 6.58 (s, 1H), 4.86 (d, J=12 Hz, 1H), 4.83-4.81 (m, 1H), 4.60 (d, J=12 Hz, 1H), 3.99-3.84 (m, 1H), 3.82 (s, 3H), 3.78-3.74 (m, 1H), 1.91-1.52 (m, 6H). 13C NMR (100 MHz, CDCl3): 159.5, 150.7, 141.8, 133.0, 132.7, 130.9, 130.8, 130.6, 128.1, 127.1, 114.7, 107.7, 98.6, 63.2, 62.6, 60.8, 55.9, 30.9, 25.8, 21.4, 19.7, 14.6.
